Systematic high resolution nuclear magnetic resonance studies will be undertaken on asymetric thyroid hormones and analogs to investigate the effects of environment on molecular conformation and to correlate stereochemistry with biological activity. The compounds to be studied are triiodothyropropionic acid, triiodothyronine, and isopropyl-diiodothyronine. X-ray crystallographic structure determinations will also be undertaken on some "fixed conformation" thyroid hormone analogs and some diphenyl ethers related to triidothyronine. These studies are designed to be complementary to the NMR work, and together with molecular orbital calculation should yield definitive answers to questions concerning preferred conformations for triiodothyronine in many environments. X-ray crystallographic structure determinations will also be performed on 3',5',3-triiodothyronine (reverse T3), 3',5',3-triiodothyropropionic acid (reverse T3P), and 3'-isopropyl-3,5,5'-triiodothyronine (IpT3). These studies should be very useful in more clearly illuminating the mechanism of action of the thyroid hormones, and thyroid hormone inhibitors. Molecular structure studies will be undertaken on two clinically important polypeptide hypothalamic hormones, thyrotropin releasing hormone (TRH) and somatostatin and some of their analogs. These studies are designed to elucidate three-dimensional features of these powerful hormones' molecular parameters and yield information which may be important in their respective mechanisms of action. Crystallographic studies of oligonucleotides and oligonucleotide complexes will be performed which will elucidate molecular information for these smaller molecules which can be usefully applied to macromolecular polynucleotides. The crystal structure of hydrated crystals of 2-p-toluidinyl-6-naphthalene sulfonate (TNS) will be determined to identify the molecular determinants and mechanism of fluorescence for this type of fluorescent probe.